The role of acetylcholinesterase in denervation supersensitivity in the frog cardiac ganglion.

1. The sensitivity of normal and denervated cardiac ganglion cells to the cholinergic agonists acetylcholine and carbamylcholine (carbachol) were compared in the frog, Rana pipiens. Acetylcholine and carbachol bind to the same acetylcholine receptors, but, unlike acetylcholine, carbachol is resistant to hydrolysis by acetylcholinesterase. 2. Sensitivity was assessed by the peak depolarization elicited in response to a sustained pulse of ligand emitted from a pipette positioned 10 microns from the ganglion cell surface. This technique allows the sensitivity of the entire cell to be recorded with a single measurement. 3. The acetylcholine sensitivity of normal cardiac ganglion cells was increased by inhibiting extracellular acetylcholinesterase with echothiophate. 4. Denervation increased the sensitivity of cardiac ganglion cells to acetylcholine but not to carbachol. 5. Following the inhibition of extracellular acetylcholinesterase with echothiophate, sensitivity to acetylcholine was similar in normal and in denervated ganglion cells. 6. The increased sensitivity to acetylcholine of cardiac ganglion cells following denervation is caused by a reduction in the hydrolysis of the transmitter by acetylcholinesterase rather than by changes in the number and/or properties of acetylcholine receptors.